i) The Phase 1 objectives are to develop and validate prototype components that may be readily integrated to create an instrument designed to meet the specifications defined by the NCATS Contract RFP. ii) B1-Microtiter plates commonly used for high throughput screening include 96 well (8x12), 384 well (16x24) or 1536 well (32x48) plates. The plates generally share common overall external dimensions (128 mm long x 85.5 mm wide - defined by the SBS Standard), with wells centered on a square grid spacing that subdivides the 96-well center-to-center distance (9mm) by a factor of 2 and 4 to generate the well center spacing for the 384 well and 1536 well plates, respectively. The major practical effect of the modulo-two subdivision of the well spacing is that multigang automatic pipetting instruments designed, for example, with 8 or 12 pipettes arranged with a linear spacing of 9mm suitable for 96-well plates, can also be programmed to pipette to 384 or 1536 well plates by programming a simple offset. Similarly, a pipetting head or pin tool able to simultaneous access 384 wells can be programmed by offset to work with a 1536-well plate. Interoperability of the prototype between the formats will be achieved. Although the cleaning requirements for plates may differ depending on end use application, the ideal objective is to create a device that is capable of cleaning all varieties of plate types to an equally high standard to allow maximum operational flexibility without risking assay quality. The cleaning process should, as far as possible, preserve key optical and all other physical features of the plate that influence assay repeatability (e.g. transparency for bottom-read plates, dimensional preservation for close-fitting PCR plates,etc.) The test plan will confirm the ultility of the prototype components to work with all plate types. iii) B-2 In order to minimize liquid wash waste the prototype will utilize a two-stage cleaning process that uses a relatively simple wash/rinse process with multiple cleaning solutions to remove 90-95% of the plate contaminants, followed by a dielectric plasma treatment. This design is an efficient and cost-effective approach for high quality HTS plate cleaning applications. This approach is selected because the effectiveness of washing declines with concentration and plasma cleaning increases in effectiveness with declining concentration. 0ptimizing the use of the two processes provides a dramatically enhanced level of cleaning irrespectiveof the chemical nature of the contaminating molecules. The proposal did not specify a metric to be measured regarding wash volumes but the testing plan proposed provides extensive testing to determine minimum volumes that will achieve the benchmark for cleaning. iv) B-3 The proposed device separates the plate cleaning process into two steps, an initial wash/rinse cycle (described below), followed by a separate plasma cleaning operation. During the later step, the energy in the plasma vaporizes any remaining solvent on the plate and the gas phase of the solvent is vented. Design optimization will be reached when the plates are dry. The testing plan provides extensive testing to determine the minimum time to achieve this benchmark based on the applications tested. v) B-4 The entire process will subject the microplates to only liquid spray or a stream of plasma gas. The plan will only use this design paradigm. vi) B-5 Cycle process time will be less than 5 minutes. This is being tested and optimized in B-2 and B-3. vii) B-6 A rigorous set of assays have been selected that include the removal to over 99% of a biological reagent, removal to over 99% of a chemical compound and several other assays that will enhance the market appeal of the system and also testing plates for a minimum useful life with no degradation at 50 cycles and tests that provide a plan to quantify a Sterility Assurance Level. Data from all testing will be included in progress reports and the Phase 1 Final Report. viii) B-7 A cost estimate has been provided for preliminary production in our proposal and during Phase 1 that estimate will be refined for low volume production. We will also provide a cost estimate to produce the unit at estimated unit quantities once on the market, which is an important benchmark for commercialization.